Phytomedicine最新文献

{"title":"Novel anti-inflammatory compounds that alleviate experimental autoimmune encephalomyelitis","authors":"Mengjiao Sun ,&nbsp;Ning Liu ,&nbsp;Jing Sun ,&nbsp;Wenjing Zhang ,&nbsp;Panpan Gong ,&nbsp;Manxia Wang ,&nbsp;Zhenxing Liu","doi":"10.1016/j.phymed.2025.156544","DOIUrl":"10.1016/j.phymed.2025.156544","url":null,"abstract":"<div><h3>Background</h3><div>Multiple sclerosis (MS) is an autoimmune disease primarily characterized by inflammatory demyelination. Despite significant research efforts, effective therapies for MS remain limited. Drug screening offers a promising approach to rapidly identifying potential therapeutic compounds.</div></div><div><h3>Purpose</h3><div>This study aimed to screen compounds that can exert anti-inflammatory effects and alleviate experimental autoimmune encephalomyelitis (EAE), an animal model of MS.</div></div><div><h3>Study design</h3><div>A fundamental research <em>in vitro</em> and <em>in vivo</em>. A high-throughput screen was performed to screen drugs that can mitigate EAE and the molecular mechanism was explored.</div></div><div><h3>Methods</h3><div>Based on our previous research highlighting the crucial role of AXL, a receptor tyrosine kinase, in microglial function, we constructed an AXL-GFP reporter gene in BV2 microglia cells. A high-throughput screen of an FDA-approved compound library was performed to identify potential AXL-targeting compounds. The effects of candidate compounds on cellular morphology, cell cycle, apoptosis, mitochondrial function, inflammatory cytokine production, polarization, and phagocytic activity of BV2 cells were assessed. To investigate the <em>in vivo</em> effects of AXL modulation, EAE mice were generated. AXL was either upregulated using recombinant Gas6 protein or knocked out using CRISPR/Cas9. The impact of AXL modulation on disease progression and underlying molecular mechanisms was explored.</div></div><div><h3>Results</h3><div>Primary and secondary screenings identified three potential AXL-targeting compounds: Betulin, Clofibric acid, and Isosorbide. Molecular docking analysis revealed that Isosorbide exhibited poor binding affinity with AXL at the molecular level and was excluded from further studies. Betulin and Clofibric acid were found to promote M2 polarization, reduce inflammation, enhance phagocytosis, extend the S phase of the cell cycle, inhibit apoptosis, and improve mitochondrial structure in BV2 cells. <em>In vivo</em> studies demonstrated that Betulin (20 mg/kg) alleviated EAE, while <em>AXL</em> gene knockout reversed its protective effects.</div></div><div><h3>Conclusion</h3><div>This study elucidates the molecular mechanism underlying Betulin's therapeutic effects in MS, both <em>in vitro</em> and <em>in vivo</em>. Betulin exerts its beneficial effects by upregulating the AXL/SOCS3 pathway and inhibiting the JAK2/STAT1 signaling pathway. These findings suggest that Betulin holds significant promise as a potential therapeutic agent for multiple sclerosis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156544"},"PeriodicalIF":6.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the therapeutic potential of HAPC in COVID-19-induced acute lung injury","authors":"Zhichen Pu ,&nbsp;Lingling Li ,&nbsp;Yan Zhang ,&nbsp;Yinping Shui ,&nbsp;Jun Liu ,&nbsp;Xiaohu Wang ,&nbsp;Xiaogan Jiang ,&nbsp;Liqin Zhang ,&nbsp;Hui Yang","doi":"10.1016/j.phymed.2025.156563","DOIUrl":"10.1016/j.phymed.2025.156563","url":null,"abstract":"<div><h3>Background</h3><div>Acute lung injury (ALI) is one of the critical complications of coronavirus disease 2019 (COVID-19), which significantly impacts the survival of patients.</div></div><div><h3>Purpose</h3><div>In this study, we screened COVID-19-related target genes and identified and optimized potential drugs targeting these genes for the treatment of COVID-19.</div></div><div><h3>Study design</h3><div>In this study, bioinformatic analyses were conducted and subsequently identified and optimized potential drugs targeting these genes for the treatment of COVID-19 were carried out.</div></div><div><h3>Methods</h3><div>Firstly, we analyzed the targets gene in patients with COVID-19 using single-cell data analysis. We performed structural modifications on Chicoric acid (CA) and combined it with hyaluronic acid to enhance the targeted activity towards Cluster of differentiation 44 (CD44). Poly (sodium-p styrenesulfonate) (PSS) was used to form a PSS-coated CA+hyaluronic acid nanocomplex (HA-P). Subsequently, <em>Lactobacillus murinus</em> conidia cell wall (CW) was encapsulated to prepare PSS-coated CA + hyaluronic acid + Lactobacillus murinus conidia cell wall (HAPC) nanocomplexes.</div></div><div><h3>Results</h3><div>The expression of APPL1 expression in macrophage of COVID-19 patients was up-regulation. CA was found to bind to the APPL1 protein and inhibit its ubiquitination. HAPC effectively targeted ALI through the highly efficient interaction between CD44 and Hyaluronic acid (HA). HAPC alleviated the symptoms of ALI and restored epithelial function in mice with ALI. HAPC induced the Adaptor protein containing a pH domain, PTB domain and leucine zipper motif 1 (APPL1)/ liver kinase B1 (LKB1)/ AMP-activated protein kinase (AMPK) pathway by inactivating the NOD - like receptor protein 3 (NLRP3) pathway in ALI. CA interacted with the APPL1 protein and prevented its ubiquitination. HAPC facilitated the interaction between APPL1 and LKB1 to induce the AMPK/NLRP3 pathway. It promoted the formation of LKB1 at GLU-67, ARG-72, ARG-314, ASP-316, and GLN-312 and APPL1 at ARG-106, ASP-115, LYS-124, ASN-119, and GLU-120.</div></div><div><h3>Conclusion</h3><div>Altogether, HAPC nanocomplexes exerted anti-inflammatory effects on ALI by promoting the interaction between APPL1 and LKB1 to induce the AMPK/NLRP3 pathway, and may be one new therapeutic strategie for ALI.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156563"},"PeriodicalIF":6.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hua Zheng San Ji Fang suppresses liver cancer progression by inhibiting TYRO3 expression via the ERK signaling pathway","authors":"Zhuang Xiong ,&nbsp;Xiaodan Sui ,&nbsp;Yu Bai ,&nbsp;Yangyang Liu ,&nbsp;Yan Leng ,&nbsp;Song Wang ,&nbsp;Boyang Su ,&nbsp;Zhiyuan Liu ,&nbsp;Tiejun Liu","doi":"10.1016/j.phymed.2025.156497","DOIUrl":"10.1016/j.phymed.2025.156497","url":null,"abstract":"<div><h3>Background</h3><div>Liver cancer poses a significant global health challenge owing to its increasing incidence and associated mortality rates. Traditional Chinese Medicine (TCM) has garnered attention for its potential in oncology, with formulations such as Hua Zheng San Ji Fang (HZSJF) exhibiting antineoplastic effects. HZSJF is clinically employed in China for cancer treatment; however, its molecular mechanisms in liver cancer remain elusive. TYRO3 plays a key role in tumor progression via the ERK signaling pathway, rendering it a potential therapeutic target. However, the effect of HZSJF on TYRO3 expression and its downstream signaling in liver cancer remains unexplored.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the molecular mechanisms through which HZSJF alleviates liver cancer progression, focusing on its regulation of TYRO3 and the ERK signaling pathway.</div></div><div><h3>Methods</h3><div>TYRO3 expression in liver cancer and para-carcinoma tissues was analyzed using immunohistochemistry, reverse transcription-quantitative PCR, and western blotting. Liver cancer cells were used to investigate HZSJF-regulated pathways. Transcriptome sequencing was used to identify HZSJF-targeted genes. Cell proliferation, apoptosis, invasion, and migration were assessed using EdU, YO-PRO-1/PI staining, and transwell assays. ERK signaling involvement was examined using a specific inhibitor and validated <em>in vivo</em> using subcutaneous nude mouse tumor models.</div></div><div><h3>Results</h3><div>HZSJF significantly inhibited TYRO3 expression and ERK pathway activation, reducing proliferation, invasion, and migration while promoting apoptosis. The ERK inhibitor corroborated the pathway's role in the antitumor effects of HZSJF. HZSJF suppressed tumor growth and TYRO3 expression <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>HZSJF alleviated liver cancer progression through the ERK signaling pathway by inhibiting TYRO3 expression, presenting a potential therapeutic approach.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156497"},"PeriodicalIF":6.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of Shexiang Baoxin Pill in patients with angina and non-obstructive coronary arteries: A multicenter, randomized, double-blind, placebo-controlled, phase Ⅳ clinical trial","authors":"Zhiqing He ,&nbsp;Na Li ,&nbsp;Wei Zhang ,&nbsp;Xianhao Meng ,&nbsp;Jingping Wang ,&nbsp;Lihong Gong ,&nbsp;Bing Liu ,&nbsp;Mingqi Zheng ,&nbsp;Zhuo Shang ,&nbsp;Jianjiang Xu ,&nbsp;Piqiao Jiang ,&nbsp;Qingxia Zhao ,&nbsp;Boning Xu ,&nbsp;Chun Liang","doi":"10.1016/j.phymed.2025.156556","DOIUrl":"10.1016/j.phymed.2025.156556","url":null,"abstract":"<div><h3>Introduction</h3><div>Solid evidence generated from large studies supporting the recommendation of Shexiang Baoxin Pill (MUSKARDIA) as a promising treatment for angina and nonobstructive coronary arteries (ANOCA) populations is lacking.</div></div><div><h3>Objective</h3><div>To evaluate the efficacy and safety of MUSKARDIA in patients with ANOCA.</div></div><div><h3>Methods</h3><div>In this randomized, double-blind, placebo-controlled, phase IV trial, we enrolled 239 patients with ANOCA at 11 centers across China between May 2021 and July 2023. Patients were randomly assigned in a 1:1 ratio to receive MUSKARDIA or placebo (orally 4 pills thrice daily) based on conventional treatment for 12 weeks. The primary endpoint was the change in angina-related outcomes, assessed using the Seattle Angina Questionnaire (SAQ) scores for the treatment groups at week 12.</div></div><div><h3>Results</h3><div>Among 239 randomized patients with ANOCA, 236 (MUSKARDIA group, <em>n</em> = 117; placebo group, <em>n</em> = 119) completed treatment and endpoint assessments. At week 12, patients in the MUSKARDIA group showed better angina-related outcomes, with a more rapid increase in SAQ scores, than those in the placebo group (all <em>p</em> &lt; 0.0001). Statistically significant differences favoring MUSKARDIA over placebo were observed for change in angina attack frequency compared with baseline at week 12 (<em>p</em> &lt; 0.0001). Meanwhile, according to the Canadian Cardiovascular Society grading of angina, the change in angina pectoris severity, compared with baseline, was significantly reduced in MUSKARDIA group compared with placebo group at week 12 (<em>p</em> &lt; 0.0001). The percentage of patients who did not use sublingual nitroglycerin was noticeably higher in MUSKARDIA group than that in placebo group (84.16 % <em>vs.</em> 58.33 %; <em>p</em> &lt; 0.001). The incidence of adverse events did not differ significantly between the two groups, and no serious adverse events occurred.</div></div><div><h3>Conclusion</h3><div>This randomized, placebo-controlled clinical trial firstly confirmed that MUSKARDIA was an effective, safe, and well-tolerated treatment for patients with ANOCA in clinical settings. This study was registered at ClinicalTrials.gov (NCT04897126).</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156556"},"PeriodicalIF":6.7,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allicin alleviates traumatic brain injury-induced neuroinflammation by enhancing PKC-δ-mediated mitophagy","authors":"Yue Cheng ,&nbsp;Wei Gu ,&nbsp;Xuechao Wu ,&nbsp;Wei Tian ,&nbsp;Zhenqian Mu ,&nbsp;Yangfan Ye ,&nbsp;Honglu Chao ,&nbsp;Zhongyuan Bao","doi":"10.1016/j.phymed.2025.156500","DOIUrl":"10.1016/j.phymed.2025.156500","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Traumatic brain injury (TBI) leads to neuroinflammation, which is a key contributor to the negative prognosis in TBI patients. Recent evidence indicates that allicin can prevent neuronal injury after TBI. However, whether allicin alleviates neuroinflammation by promoting mitophagy is unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;We investigated the suppressive effects of allicin on neuroinflammation and clarified the role of mitophagy in the underlying mechanism.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study design/methods&lt;/h3&gt;&lt;div&gt;The controlled cortical impact (CCI) was employed to effectively mimic TBI in a living system. Cellular mechanical damage was modeled in vitro using a Bv2 cell stretch model. Neuroinflammation was assessed by evaluating levels of TNF-α, IL-1β, IL-6, ROS, IL-4 and IL-10, along with the expression of NLRP3 and TLR4 proteins. RNA-sequence and KEGG analyses revealed allicin-regulated molecular processes in the Bv2 cell stretch model. Immunofluorescence staining was performed to label both the autophagy marker protein LC3 and the outer mitochondrial membrane (OMM) marker COX IV. Lipid MS and lipidomic analyses were used to determine the CL levels in the OMM and IMM. The characteristic bilayer structure of mitochondria was observed using transmission electron microscopy (TEM). PKC-δ expression and phosphorylated phospholipid scramblase-3 (PLS3) levels were detected via western blotting. Stretched Bv2 cells and primary neurons were cocultured to assess the anti-neuroinflammatory effects of allicin. Neuro-rehabilitation was assessed using behavioral experiments such as the rotarod and morris water maze (MWM) tests.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Allicin treatment reduced TNF-α, IL-1β, IL-6, ROS levels, and the expression of NLRP3 and TLR4 proteins in mice with CCI, while IL-4 and IL-10 levels remained unchanged. Additionally, allicin reduced tissue lesions and cell death after CCI. The transcriptomic analysis revealed that mitophagy was important in allicin-related molecular pathways. The translocation of CL from IMM to OMM was facilitated by allicin, as demonstrated by flow cytometry and lipidomic analyses. Importantly, allicin increased PKC-δ expression and PLS3 phosphorylation in the CL-related mitophagy process in both the CCI and Bv2 cell stretch models. These findings suggest that allicin reduces mitophagy-related neuroinflammation and further prevents neuronal injury in vitro. Rottlerin, a selective PKC-δ inhibitor, effectively diminished allicin's capacity to reduce neuroinflammation, correlating with worsened motor function and cognitive abilities. Thus, CCI-induced behavioral deficits were also ameliorated by the administration of allicin via a PKC-δ-related mitophagy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;This study uncovers a novel mechanism where allicin enhances PKC-δ expression and PLS3 phosphorylation, facilitating CL translocation to the OMM and activating mitophagy, thereby reducing TBI-indu","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156500"},"PeriodicalIF":6.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Notoginsenoside R1 reduces acquired lymphedema and increases lymphangiogenesis by promoting VEGF-C expression via cAMP/PKA/CREB signaling","authors":"Jia-Min Bao ,&nbsp;Tong Hou ,&nbsp;Li Zhao ,&nbsp;Yong-Jia Song ,&nbsp;Yang Liu ,&nbsp;Lian-Ping Xing ,&nbsp;Hao Xu ,&nbsp;Xiao-Yun Wang ,&nbsp;Qing Li ,&nbsp;Li Zhang ,&nbsp;Jun-Li Chang ,&nbsp;Wei Li ,&nbsp;Qi Shi ,&nbsp;Yong-Jun Wang ,&nbsp;Qian-Qian Liang","doi":"10.1016/j.phymed.2025.156554","DOIUrl":"10.1016/j.phymed.2025.156554","url":null,"abstract":"<div><h3>Background</h3><div>Acquired lymphedema is a global health concern with limited treatment options. While vascular endothelial growth factor C (VEGF-C) administration has shown promise for the treatment of this patient population, no small-molecule compounds have hitherto been identified to improve lymphedema by stimulating VEGF-C expression and lymphangiogenesis.</div></div><div><h3>Objective</h3><div>This study investigated the therapeutic effect of notoginsenoside R1 (R1) on a mouse model of tail acquired lymphedema and explored the underlying mechanisms.</div></div><div><h3>Methods</h3><div>C57BL/6J mice and lymphatic endothelial cells (LECs) specific VEGFR-3 knockout transgenic mice underwent surgical induction of tail acquired lymphedema. Tail circumference, lymphatic drainage function, VEGF-C expression, and lymphangiogenesis were measured. LECs’ function was assessed using wound healing and tube formation assays. Quantitative PCR (q-PCR) and western blot were conducted to measure VEGF-C expression levels. In addition, RNA sequencing analysis and western blot were performed to elucidate the signal pathways involved. Luciferase reporter assays assessed VEGF-C promoter activity.</div></div><div><h3>Results</h3><div>R1 treatment improved lymphedema, lymphatic function, and lymphangiogenesis in the mouse model. R1 enhanced migration, tube formation, and VEGF-C expression of LECs. These effects were abolished by VEGF-C siRNA and VEGFR-3 inhibitors. VEGFR3 knockout in LECs completely blocked R1′s ability to promote lymphangiogenesis and lymphatic drainage while partially but significantly reducing its improvement on lymphedema. R1 activated the cAMP/PKA signaling pathway, leading to PKA and CREB phosphorylation. The PKA inhibitor and CREB siRNA inhibited R1-induced VEGF-C expression. Additionally, R1 activated VEGF-C promoter activity in a CREB-dependent manner.</div></div><div><h3>Conclusion</h3><div>R1 emerges as the first reported small natural compound to promote VEGF-C expression. It reduces acquired lymphedema and enhances lymphangiogenesis via the cAMP/PKA/CREB signaling pathway. These findings suggest R1 as a potential novel oral medication for treating acquired lymphedema patients.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156554"},"PeriodicalIF":6.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin attenuated necroptosis and apoptosis caused by LPS-induced mitochondrial function dysfunction through the METTL3-mediated PTEN m6A methylation/PI3K/AKT signaling in broiler livers","authors":"Yu Xia ,&nbsp;Yidan Wang ,&nbsp;Kai Chen ,&nbsp;Muyue Zhang ,&nbsp;Qihang Jiang ,&nbsp;Tong Xu","doi":"10.1016/j.phymed.2025.156551","DOIUrl":"10.1016/j.phymed.2025.156551","url":null,"abstract":"<div><h3>Background</h3><div>Quercetin (QUE), a natural flavonoid, offered an efficient protection against organism injury. N6-methyladenosine (m⁶A) methylation is considered to be the most prevalent and abundant modifications involved in various diseases.</div></div><div><h3>Purpose</h3><div>We sought to explore protective roles of QUE in mitigating necroptosis and apoptosis triggered by LPS-induced imbalances in mitochondria dynamic and energy metabolism in broiler livers, with a focus on m⁶A methylation modulation.</div></div><div><h3>Study design/Methods</h3><div>We used LPS as a stimulus and treated with QUE to establish this <em>in vivo</em> and <em>in vitro</em>. In addition, we treated LMH cells with siMETTL3 (80 nM) to determine its detailed mechanism.</div></div><div><h3>Results</h3><div>Our findings revealed QUE significantly decreased METTL3 expression, leading to a decrease in PTEN m⁶A methylation and factors related to mitochondria fission, necroptosis, and apoptosis in the QUE+LPS group. In contrast, QUE treatment promoted the expression levels of marker factors for mitochondria fusion, energy metabolism, anti-apoptosis, and PI3K/AKT compared with the LPS group. Additionally, an increase of ΔΨm, ATP content, and ATPase activity was observed. AO/EB staining, Flow cytometry and TUNEL assays confirmed QUE inhibited LPS-induced apoptosis and necroptosis. Molecular docking analysis and cellular thermal shift assay supported an interaction between QUE and METTL3.</div></div><div><h3>Conclusion</h3><div>In summary, QUE mitigated necroptosis and apoptosis triggered by LPS-induced disorders of mitochondrial kinetic and metabolic processes in broiler livers through its interaction with METTL3, regulating PTEN m⁶A methylation/PI3K/AKT signaling pathway. This study enhances our understanding of biological functions for QUE and lays a theoretical foundation for developing new therapeutic interventions, highlighting its potential value.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156551"},"PeriodicalIF":6.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clematichinenoside AR alleviates rheumatoid arthritis by inhibiting synovial angiogenesis through the HIF-1α/VEGFA/ANG2 axis","authors":"Meiling Yuan ,&nbsp;Yajie Wu ,&nbsp;Xinyue Zhou ,&nbsp;Yikang Cai ,&nbsp;Hui Li ,&nbsp;Aixin Xia ,&nbsp;Xiao Wang ,&nbsp;Jianting Wen ,&nbsp;Qiangjun Duan ,&nbsp;Chenhao Xu ,&nbsp;Huibo Cao ,&nbsp;Chenggui Miao","doi":"10.1016/j.phymed.2025.156552","DOIUrl":"10.1016/j.phymed.2025.156552","url":null,"abstract":"<div><h3>Background</h3><div>Clematichinenoside AR (CAR) is an effective monomer component of <em>Clematis chinensis Osbeck</em>, which has therapeutic effects on rheumatoid arthritis (RA), but its specific mechanism is still not fully elucidated.</div></div><div><h3>Purpose</h3><div>This study elucidated whether CAR alleviated RA by inhibiting synovial angiogenesis and revealed its molecular mechanism.</div></div><div><h3>Methods</h3><div>Arthritis indicators and H&amp;E staining were used to evaluate the therapeutic effects of CAR on collagen-induced arthritis (CIA) rats, and the IHC, IF, EdU-Hoechst, tunel, flow cytometry, wound healing and transwell assay were used to investigate the effects of CAR on synovial angiogenesis. The co-culture model of RA fibroblast-like synoviocytes (FLSs) and human umbilical vein endothelial cells (HUVECs) was established. Tube formation, western blot, RT-qPCR and other related methods were used to evaluate the specific mechanism of CAR.</div></div><div><h3>Results</h3><div>CAR alleviated arthritis pathology and inhibited angiogenesis in CIA rats. CAR inhibited the proliferation, migration and invasion of RA FLSs, and promoted their apoptosis. Importantly, overexpression of HIF-1α inversed the inhibitory impact of CAR on the expression of HIF-1α, VEGFA, VEGFR2, and ANG2, as well as the inhibitory effects of CAR on the expression of CD31/34 and the HUVEC tube formation. Molecular docking, molecular dynamics, and experimental verification confirmed that CAR has a strong binding affinity with HIF-1α, further indicating that HIF-1α was a target of CAR for anti-angiogenesis.</div></div><div><h3>Conclusion</h3><div>CAR had a good inhibitory effect on RA, and its mechanism was inhibition of synovial angiogenesis through the HIF-1α/VEGF/ANG2 axis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156552"},"PeriodicalIF":6.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triterpenoids from ilicis rotundae cortex ameliorate hyperlipidemia by affecting bile acids-hepatointestinal FXR axis","authors":"Wei Zeng ,&nbsp;Mengjia Sun ,&nbsp;Jiamin Cao ,&nbsp;Caixin Chen ,&nbsp;Shiqin Jiang ,&nbsp;Yuanyuan Wang ,&nbsp;Weiqun Yang ,&nbsp;Zhongxiang Zhao ,&nbsp;Jing Jin","doi":"10.1016/j.phymed.2025.156537","DOIUrl":"10.1016/j.phymed.2025.156537","url":null,"abstract":"<div><h3>Background</h3><div>Hyperlipidemia is a lipid metabolism disorder that, in severe cases, can lead to conditions such as hypertension, coronary heart disease, and cirrhosis. Previous studies have identified Ilicis Rotundae Cortex (IRC) crude extract as having the potential to regulate blood lipids. However, whether the triterpenoids therein are the principal agents responsible for hypolipidemic effects and their specific mechanisms of action remain unexplored. This study aimed to investigate the effects of total triterpenoids (TT) extract derived from IRC on hyperlipidemia and to elucidate their potential mechanisms.</div></div><div><h3>Methods</h3><div>TT extract was first prepared and characterized to assess their hypolipidemic activity in cell models. A hyperlipidemia mouse model was established by using C57BL/6 J mice fed a high-fat, high-sugar, and high-cholesterol diet for 8 weeks. TT extract was administered as a prophylactic intervention for 4 weeks to evaluate its impact on blood lipid levels, liver lipid metabolism, and liver function. Based on progressive analysis, this study integrated serum non-targeted metabolomics analysis strategy and bile acids-targeted metabolomics analysis strategy. It was combined with modern molecular biology techniques to reveal the mechanism by which TT extract ameliorated the symptoms of hyperlipidemia through a cascade approach.</div></div><div><h3>Results</h3><div>TT extract treatment significantly reduced lipid levels in hyperlipidemic mice. Notably, TT extract down-regulated bile acid levels, particularly bile acids as FXR antagonists such as T-β-MCA, β-MCA, TUDCA, and UDCA. This effect is likely mediated through alterations in the hepatic FXR-SHP and ileal FXR-FGF15 signaling pathways. TT extract administration led to decreased expression of CYP7A1 and CYP7B1, resulting in reduced bile acid levels in <em>vivo</em>. Additionally, FXR expression was upregulated in both the liver and ileum, potentially activating FGF15 in the ileum, which in turn transmits signals to the liver and modulates SHP and BSEP expression. These changes contribute to the regulation of bile acid synthesis, metabolism, and excretion. In <em>vitro</em> experiments also demonstrated that TT extract influenced the protein expression of FXR and FGF19.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that TT extract from IRC has hypolipidemic effects. This study is the first to reveal the mechanism by which TT extract improves hyperlipidemia from the perspective of the hepatic-intestinal axis and bile acid metabolism. Its underlying mechanism is related to activating the intestinal FXR-FGF15/19 signaling pathway, which transmits signals to the liver, thereby affecting the hepatic FXR-SHP signaling pathway. This results in improved bile acid metabolism, ultimately reducing hepatic injury and ileal inflammation to exert hypolipidemic effects.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156537"},"PeriodicalIF":6.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Jinkui Shenqi decoction targets PAD4 to restrain NETosis and ameliorates psoriasis progression","authors":"Wanjun Zhao ,&nbsp;Xiaoyan Liu ,&nbsp;Jianing Tang ,&nbsp;Jieyu Chen ,&nbsp;Dong Liu ,&nbsp;Haiyan Sun ,&nbsp;Jiao Qu ,&nbsp;Yang Sun ,&nbsp;Zijun Ouyang","doi":"10.1016/j.phymed.2025.156543","DOIUrl":"10.1016/j.phymed.2025.156543","url":null,"abstract":"<div><h3>Background</h3><div>The underlying pathogenesis of psoriasis was attributed to insufficient kidney qi and blood stasis arising from impeded blood circulation. Jinkui Shenqi decoction (JKSQD), was renowned for its capacity to warm and tonify kidney yang, as well as to invigorate blood circulation. However, there remains a dearth of studies on its specific therapeutic effects and underlying mechanisms of psoriasis.</div></div><div><h3>Purpose</h3><div>Aiming to investigate the effectiveness and mechanism of JKSQD in the treatment of psoriasis.</div></div><div><h3>Methods</h3><div>Initially, we identified the compounds of JKSQD by UPLC-Q-TOF-MS/MS and constructed psoriasis-like mice to explore the effect of JKSQD on psoriasis. Subsequently, proteomic sequencing was conducted to identify key proteins and pathways involved in the therapeutic effect of JKSQD. Neutrophil extracellular traps (NETs) and peptidylarginine deiminase 4 (PAD4)-related indicators were detected to validate JKSQD mechanisms. At last, we analyzed metabolomic data to elucidate what metabolic pathway or metabolites worked during this procedure.</div></div><div><h3>Results</h3><div>We found that JKSQD effectively reversed the progression of psoriasis and associated inflammation in mice. Proteomic analysis further illuminated that PAD4 involved in NETosis was notably downregulated in psoriasis-like mice after JKSQD treatment. And a series of experiments further revealed that JKSQD inhibited NETs formation and PAD4 expression. Moreover, metabolomics demonstrated JKSQD influenced D-Arginine and D-ornithine metabolism, offering deeper insights into the mechanisms of JKSQD on psoriasis.</div></div><div><h3>Conclusions</h3><div>This study unveiled that JKSQD could improve psoriasis progression by targeting PAD4 to inhibit NETs formation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156543"},"PeriodicalIF":6.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}